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Targeting Cardiovascular Disease with Microbiota-derived Bioactive Compounds

Project description

Gut microbiota metabolites against cardiovascular disease

The gut microbiome helps digest the food that we eat but also supports overall health. Recent evidence indicates that the gut microbiome is associated with metabolic conditions such as obesity and type 2 diabetes. At the same time, it is known to produce beneficial compounds like polyphenols with antioxidant and anti-inflammatory properties. With the support of the Marie Skłodowska-Curie Actions programme, the DIETherapy project aims to identify the link between the gut microbiome and cardiovascular diseases. Researchers will identify polyphenolic metabolites associated with lower atherosclerosis risk and assess their potential to reprogramme immune cells towards an anti-inflammatory phenotype. The ultimate goal is to set the stage for advancing microbiome-based strategies to prevent and treat cardiovascular diseases.

Objective

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, although advancements in glucose-lowering, weight-reducing, and lipid-lowering therapies. Emerging evidence suggests that the gut microbiome and its metabolites are critically involved in the pathogenesis of various metabolic disorders contributing to CVDs, including obesity and type 2 diabetes, and also play a direct role in CVD development. Conversely, other reported microbiome-derived compounds appear to be beneficial for the host, exhibiting antioxidant and anti-inflammatory properties. This project aims to explore the therapeutic potential of microbiota-derived polyphenols in modulating the immune system to prevent and treat CVDs. Specifically, this proposal seeks to identify polyphenolic metabolites associated with a reduced risk of atherosclerosis development and to assess their immunomodulatory and protective effects in murine models. Aim 1 will involve bioinformatic analyses of a large human cohort with comprehensive microbiome and metabolome data to identify polyphenolic candidates associated with a lower risk of atherosclerosis. Aim 2 will explore the capacity of these polyphenols to induce long-term anti-inflammatory phenotypes through epigenetic and transcriptomic reprogramming in human and murine innate immune cells (trained immunity). The therapeutic efficacy of these polyphenols will be further evaluated in murine models of atherosclerosis and chronic inflammation, with a focus on elucidating the underlying molecular mechanisms. The methodologies employed will include advanced bioinformatics, in vitro immune cell assays, and in vivo murine studies, including microbiota and metabolome profiling. This interdisciplinary approach, combining human clinical data with mechanistic studies in mice, is expected to provide new insights into the role of microbiota-derived polyphenols in CVD prevention and treatment, potentially leading to novel therapeutic interventions.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

GOETEBORGS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 236 340,00
Address
VASAPARKEN
405 30 Goeteborg
Sweden

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Region
Södra Sverige Västsverige Västra Götalands län
Activity type
Higher or Secondary Education Establishments
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Total cost

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